A recent study published in The Journal of Immunology has found that insufficient dietary iron can weaken the function of memory T cells in the lungs after influenza infection. Researchers investigated how a lack of iron affects the development and effectiveness of these immune cells, which are crucial for long-term protection against viruses.
The research involved feeding female mice either an iron-deficient or an iron-replete diet from weaning. Mice were kept under pathogen-free conditions and monitored at several stages: before infection, during acute influenza infection, and during memory formation. The team measured anemia through hemoglobin levels and assessed systemic iron by analyzing liver tissue.
During the experiment, all mice received a standardized dose of X31 (H3N2) influenza virus. Researchers then examined their spleens and lungs to analyze T cell numbers, phenotypes, activation markers, and cytokine production using flow cytometry.
Mice on an iron-deficient diet gained less weight and developed anemia with significantly lower liver iron levels compared to those on an iron-replete diet. While both groups had similar overall T cell counts, mice lacking sufficient dietary iron showed altered baseline T cell characteristics—such as higher expression of transferrin receptor proteins—and changes in regulatory markers.
Following primary influenza infection, mice with low dietary iron experienced more severe early illness symptoms and slower recovery. Although total lung T cell counts remained comparable between groups, those on the deficient diet had increased splenic T cell numbers early on but fewer antigen-specific lung-localized T cells at day 7 post-infection. Activation marker expression was temporarily reduced in lung CD4⁺ influenza-specific T cells among the deficient group.
At the memory stage after infection, both groups produced similar total numbers of memory T cells; however, mice fed with less iron generated more influenza-specific memory T cells in their lungs. Despite this increase in number, these memory cells—especially CD8⁺ types—showed impaired ability to produce important antiviral cytokines like TNF-α and IFN-γ when challenged again by antigens. This functional impairment persisted even when optimal antigen-presenting conditions were provided.
The researchers concluded that “dietary iron deficiency disrupts early lung T cell activation during infection and compromises the effector function of memory T cells, particularly CD8⁺ memory cells, during recall responses.” They also noted that “iron-deficient mice experienced greater illness severity, delayed early lung immune responses, and ultimately developed memory T cells with a reduced capacity to produce key antiviral cytokines.”
These findings suggest that maintaining adequate dietary iron is essential for effective long-term immunity against respiratory infections such as influenza. The effects were most pronounced in the lungs—a critical site for fighting flu viruses—and highlight how nutritional status can influence immune protection over time.
While acknowledging limitations such as not being able to fully separate intrinsic defects from environmental factors within lung tissue or distinguish between different types of resident memory cells in the lungs, researchers emphasized: “maintaining sufficient dietary iron is essential for healthy memory T cell function and robust long-term antiviral immunity.” They further stated that “these findings may have particular implications for early-life iron deficiency and for immune responses to respiratory infections and vaccines.”
